System for use in bioprocessing

ABSTRACT

A consumable container for filling with a fluid in a bioprocessing process. The container comprises one or more sealable, removable portions, such that one or more samples of the fluid may be taken by sealing and removing one or more of said portions.

RELATED APPLICATIONS

The present application is a continuation patent application of Ser. No.16/302,304, filed Nov. 16, 2018, which is a national stage applicationunder 35 U.S.C. § 371 of International Application No.PCT/GB2017/051459, filed 24 May 2017, which claims priority to GreatBritain Patent Application No. 1609084.7, filed 24 May 2016. The abovereferenced applications are hereby incorporated by reference into thepresent application in their entirety.

FIELD

The present invention relates to a system for use in bioprocessing.

BACKGROUND

In bioprocessing it is often necessary to remove a sample from a largervolume of a product, such as for analysis of the sample for the purposeof quality assurance. Because of the nature of such bioprocessing,several design constraints are imposed on systems for removing suchsamples. For example, the removal of samples must be carefullycontrolled to avoid modifying or damaging the samples, and the samplesmust be of a minimum possible volume to avoid wasting potentiallyexpensive product. Furthermore, such systems should be structured sothat the process is aseptic, to avoid contamination of the product orsamples. Many areas of biological research, for example autologous celltherapies, can also require that samples be taken at specific times, andthat any samples be traceable. Variation in timing compared to theexpected timing will lead to uncertainty over the validity of theresult. For example, in a cell expansion process, taking a sample latecould lead an incorrect assessment of the rate of expansion. A failureto ensure traceability could lead to analysing an incorrect sample. Inthe worst case this could lead to an unsafe product being declared safe.It is also desirable that such a system be low cost. Developing suchsystems therefore presents many challenges, and currently, therefore,sampling is often done manually.

One example of a manual process of removing a sample from a largervolume of a product relates to the removal of a sample from a WAVEBioreactor, as produced by GE Healthcare Life Sciences. In suchbioreactors a product is held within a disposable bag and rocked toprovide mixing and gas transfer. When a sample is taken the movement ofthe product must be stopped and the user must prepare a sample port, forexample by wiping with alcohol. The user must then connect a syringe tothe sample port and tip the product bag so that the sample may beaspirated into the syringe. The movement of the product may only berestarted after the syringe has been removed. Finally, the sample mustbe transferred from the syringe into a format suitable for processing inan analysis system, for example a vial.

Such a manual process has numerous drawbacks, however. The first ofthese is that, in order for a sample to be taken, the product movementmust be stopped, and this interruption will be for a variable period oftime, potentially leading to product variability. There are also issueswith the sampling method itself not being completely closed orcompletely controlled. As mentioned above, it is important to ensurethat the sample and product are not contaminated and that they are notdamaged. However, the interface between the syringe and the product isnot completely sealed, leading to potential contamination, and theaspiration is not completely controlled, potentially leading to damageof the product and sample. There is also the issue that the samplevolume may be larger than necessary. Additionally, the timing of thesampling is dependent on the user as the process is highly userintensive.

The present invention aims to solve this and other issues by providing ameans of taking samples of a product which is easily automated and whichis resistant to damage or contamination of the product and sample andallows for reliable traceability.

A further problem is that once the sample is taken it needs to beanalysed. Common analyses can include cell viability and cell countingthrough first staining the cells and then imaging using an appropriatesystem. Other analytical approaches will look at cell phenotype using afluorescent label and a flow cytometer. Further they can includemolecular analysis, studying a cell's DNA with PCR, or alternatively abiomarker such as protein expression by the cells by using animmuno-assay. Other assays can look for contamination such as bacterial,fungal, or viral.

Typically a sample is taken from a bioreactor, transported to an areaappropriate for sample preparation and then moved on for subsequentanalysis. When working with biological samples, this will typicallyrequire biological containment to both protect the operator and toensure the sample is not contaminated. There is variability and costassociated with both the sample transport and the analysis of the sampledue to the operator involvement. The need for containment also presentsa significant cost burden.

SUMMARY OF INVENTION

According to a first aspect of the invention, a consumable container isprovided, said consumable container for filing with a fluid in abioprocessing process and comprising one or more sealable, removableportions, such that one or more samples of the fluid may be taken bysealing and removing one or more of said portions.

In contrast to the manual process of taking samples of a product, thepresent invention ensures that, if attached to a rocking bioprocessor,the movement of said product need not be stopped to allow aspiration ofa syringe, thereby preventing product variability. The sampling is alsocompletely aseptic and controlled, preventing both contamination andproduct damage, and further ensuring that no more product is taken thanis necessary.

The consumable container is also suitable for easy automation of thesampling process. The manual process described above is difficult toautomate and is therefore highly user intensive. By allowing forautomation of the sampling, the user may focus on other tasks, and thesample may be taken at any time.

An aspect of the present invention aims to solve some of the problemsassociated with the prior art by directly coupling the analyticalprocess to the sampling process. The analytical process is oftenautomated to avoid operator variation and cost. The process isinherently “closed” to avoid contamination and safety risks.

A further benefit is that whereas previously the sample would have to betransferred from the syringe into a format suitable for processing in ananalysis system (for example a vial), or for easy transfer in a labtransport system (for example a pneumatic tube system), the presentinvention ensures that the sample may be taken in a format alreadysuitable for analysis. This helps to prevent contamination of thesample.

Different methods may be employed to seal the one or more sealable,removable portions. The one or more sealable, removable portions may besealed by application of heat to an area between the removable portionand the remainder of the consumable container, or in another embodimentthe one or more sealable, removable portions may be separated from theremainder of the consumable container by respective physical, asepticconnectors, said connectors allowing sealing and removal of respectiveassociated portions. If the portions are to be sealed by application ofheat, the consumable container will preferably comprise a heat sealablematerial.

The one or more removable portions may be connected to a commontransverse part in parallel or they may be connected in series. Samplesmay also be taken by removing portions of the bulk consumable container.

The consumable container of the present invention will preferablycomprise a biocompatible material. The consumable container may alsocomprise at least one of: ethylene-vinyl acetate (EVA), polyvinylchloride (PVC), or polyethylene (PE).

In some embodiments of the first aspect of the invention, the consumablecontainer will comprise a laminate polymer construction. For example,one layer of the laminate construction might be safe for contact withthe fluid, another might provide a gas boundary, and one might besuitable for heat sealing. This allows for combinations of differentproperties to be incorporated into the material of the consumablecontainer.

The portions removed from the consumable container may be disposedwithin respective vials, and the one or more removable portions of theconsumable container are preferably disposed within respective vialsprior to said portions being removed. Said vials will preferably haverespective lids. More preferably, the vials will be configured such thatremoval of the lid from a vial will unseal the removable portiondisposed within. According to some embodiments said vials can betransported within a pneumatic tube system. However, the format of thesample must be suitable for the analysis system being used. Therefore,the one or more removable portions may only be disposed in respectivevials if this is a format suitable for the analysis system being used.

Embodiments of the first aspect of the invention may also provide theone or more sealable, removable portions in the form of an array.However, the consumable container could also comprise a single sealable,removable portion.

Further embodiments of the first aspect of the invention provide forsampling vials, wherein the one or more sealable, removable portions areattached to respective vials prior to removal. Such embodiments avoidthe need to dispose a sample within a vial.

According to a second aspect of the invention, a consumable containerfor filling with a fluid in a bioprocessing process is provided, whichcomprises one or more sealable portions, such that one or more samplesof the fluid may be taken by sealing one or more of said portions, andwherein at least one of the sealable portions comprises an analyticsregion.

The analytics region may comprise reagents, such as lyophilisedreagents, or other features to enable analysis of the bioprocess fluidto be conducted within the sealable portion. The additional featuresmay, for example, be an optical detector, an electrochemical detector, aheating element, a cooling element, or a combination of these.

According to embodiments of the second aspect of the invention, thesealable portions may be removable.

Initially the bioprocess fluid is sealed from these reagents so that thereagents cannot come into contact with the bioprocess fluid. Suchcontact would risk contamination of the fluid, which is typically theproduct and may be infused into a patient later in the process. Thefluid can be sampled into the analytical sealable portion when required,but still sealed from the reagents. The analytical sealable portion canthen be sealed and removed from the system by any of the methodsdescribed in the previous invention. The sample is preferably broughtinto contact with the analytics region only once the sample region hasbeen sealed from the bulk fluid. This ensures that reagents in theanalytics region are kept separate from the bulk fluid, therebypreventing contamination of the bulk by the reagents.

In some embodiments this sampling will include a “loop” where the samplecan both flow into and out of the analytical sealable portion. In otherembodiments the sampling will be a “dead end” which contains a vacuum.In a further embodiment the sampling will be a “dead end” where thesampling region is compliant and initially collapsed. Filling will causethe sample region to inflate.

The analytical sealable portion can be made from rigid polymer in someembodiments. In other embodiments it may be made from thin flexiblepolymers heat sealed together. This has the advantage of eliminatingdead volumes and reducing bubbles while also being low cost. This may beattached to a rigid chassis to simplify handling. Polymers could includeethylene-vinyl acetate (EVA), polyvinyl chloride (PVC), polypropylene(PP) or polyethylene (PE)

Following removal of such embodiments from the system, the bioprocessfluid can then pass through the steps required for analysis. These stepsmay be automated to avoid user variability. The first step may bring thefluid into the analytics region. This can be achieved by breaking aseal, for example a heat seal that is sufficient to avoid opening undernormal processing pressures but when desired can be broken to allowfluid to flow past this seal. The heat seal could be broken byapplication of fluid pressure. In the “dead end” embodiment, this fluidpressure could be achieved by compressing the sample region, while inthe “loop” embodiment this could be achieved by a drive fluid connectedto the sample region. Alternatively, the separation of the fluid fromthe analytics region could be achieved by other methods, for example avalve such as a pinch valve. Another possibility is that it could beconnected to a previously separate part of the system. In embodimentswhere the sealable portions are removable, the separation of the fluidfrom the analytics region may not be broken until after the sampleregion has been separated from the main portion of the consumablecontainer.

In some embodiments of the second aspect of the invention, the one ormore sealable portions may respectively comprise a sample region havingan input end for receiving fluid and an output end, the sample regionbeing connected to the analytics region. The input end of the sampleregion may be configured to receive fluid from a main portion of theconsumable container and the output end to return fluid to said mainportion. A valve may be disposed on the main portion between the inputend of the sample region and the output end of the sample region, suchthat fluid is directed into the sample region when the valve is closed.The analytics region may be connected to the sample region via an inletdisposed between the input end of the sample region and the output endof the sample region. Alternatively, the input end of the sample regionmay be configured to receive fluid from a main portion of the consumablecontainer and the analytics region may be connected to the sample regionat the output end of the sample region. In embodiments where thesealable portions are also removable, the connection between theanalytics region and the sample region may be sealed until the sampleregion has been separated from the main portion. The sealing of theanalytics region from the sample region may achieved by a heat seal, andthe heat seal may be opened by the application of fluid pressure createdby compressing the sample region. The sealing of the analytics regionfrom the sample region may be achieved by a pinch valve. The analyticsregion may include reagents. The analytics region may includelyophilised reagents. The analytics region may include an opticaldetector. The analytics region may include an electrochemical detector.The analytics region may include a thermal (calorimetric) detector. Theanalytics region may include a heating or cooling element.

In some embodiments the fluid may be brought into contact with liquid ordry reagents which may be dyes able to stain cells within the fluid.Possible dyes include DAPI, acridine orange, trypan blue, and calceinAM, or other dyes that may be useful for staining either live cells,dead cells, or both.

In other embodiments the reagents will allow for the detection ofproteins for example through the use of an enzyme linked immunosorbentassay (ELISA).

In another embodiment the reagents will allow for a polymerase chainreaction so that the DNA can be amplified and later detected todetermine the genetic identity of material in the fluid.

In some embodiments the fluid may then be moved to a separateinterrogation region. This region may have a high optical quality toenable better detection using optical methods such as photodiodes,cameras or photo multiplier tubes. The region may be illuminated by alight source such as an LED, laser or incandescent bulb which may serveto enable the cells or other items to be observed or may cause them tofluoresce. Alternatively this detection may occur in the same locationas the fluid is mixed with the reagents. Detection could alternativelybe by electrochemical methods where electrodes functionalised withappropriate chemistry are embedded in the detection region to detect thedesired analytes. In addition, detection could be by thermal(calorimetric) methods whereby heat emitted (exothermic) or absorbed(endothermic) by the fluid detects the desired analytes or the metabolicactivity of cells.

According to a third aspect of the invention, a system is provided, thesystem including a reusable part, a bulk fluid container, and aconsumable container according to the first aspect of the invention. Theconsumable container is arranged to be fluidly connected in use to thebulk fluid container such that the consumable container may be filledwith a sample of the fluid from the bulk.

The system will preferably further comprise means for purging theconsumable container and returning the fluid to the bulk container afterthe one or more removable portions have been removed.

Fluid may in some embodiments be transferred between the bulk containerand the consumable container at least partially through the creation ofa vacuum outside the disposable. Alternatively, where at least part ofthe disposable is rigid walled, fluid may be transferred between thebulk container and the consumable container by the creation of a vacuumwithin the disposable. Fluid may, in addition or alternatively, betransferred between the bulk container and the consumable container atleast partially through the action of gravity by positioning theconsumable container below the level of the fluid in the bulk container.Another possibility is for the fluid to be transferred between the bulkcontainer and the consumable container at least partially through theuse of a pump. The pump may be a peristaltic pump.

According to a fourth aspect of the invention, a system is provided forprocessing biological samples, the system comprising a first processingstation having an outlet, a second processing station having an inlet, apumped fluidic channel connecting said outlet to said inlet, wherein thesecond processing station comprises a consumable container, wherein theconsumable container comprises one or more sealable, removable portions,such that one or more samples of the fluid may be taken by sealing andremoving one or more of said portions.

BRIEF DESCRIPTION OF THE FIGURES

Some examples of consumable containers and systems for use inbioprocessing will now be described with reference to the accompanyingdrawings, in which:-

FIG. 1 shows an arrangement of components involved in taking samples inbioprocessing;

FIG. 2 shows another arrangement of components involved in takingsamples in bioprocessing;

FIG. 3 shows still another arrangement of components involved in takingsamples in bioprocessing;

FIGS. 4a to 4d show the steps of a possible method for taking samplesfrom a consumable container;

FIGS. 5a to 5d show the steps of another possible method for takingsamples from a consumable container;

FIGS. 6a to 6d show the steps of a further possible method for takingsamples from a consumable container;

FIGS. 7a to 7d show the steps of one method for disposing a sample in avial, such that removing the lid from the vial allows access to thesample;

FIGS. 8a to 8e show the steps of an alternative method for disposing asample in a vial, wherein the vials are supplied attached to theconsumable container;

FIG. 9 shows the separable portions as part of a bioprocessing system;

FIG. 10 shows an example of a separable portion which includes ananalytics region;

FIG. 11 shows the operation of a separable portion which includes ananalytics region; and

FIG. 12 shows another example of a separable portion which includes ananalytics region, and the operation of that separable portion.

DETAILED DESCRIPTION

FIG. 1 shows an arrangement of components involved in taking samples inbioprocessing in which a sampling system 11 is connected to abioprocessing system 14. System 11 is for isolating samples for analysisand includes a consumable container 12 and a reusable part 13. Theconsumable container 12 is consumed in the process of taking samples,said process being carried out by reusable part 13. The bioprocessingsystem 14 includes a bag 15 carrying the bulk product which is to besampled, said bag having at least one sampling port 16. Thebioprocessing system 14 provides a rocking motion to allow for mixingand gas transfer within bag 15 in order to promote cell growth.

The consumable part 12 of the system 11 is connected to sampling port 16of bag 15 in the bioprocessing system 14 via a tube 17 during theinitial setup of bioprocessing system 14 and remains connected for theduration of the bag's use. The consumable part 12 of the system 11 cantake different forms, but all generally include sealable, removableportions 18. This allows for samples of the fluid to be taken by sealingand removing one of the portions 18.

In the system depicted in FIG. 1, the consumable 12 is initially emptyof any liquid or gas, and fluid is transferred from bag 15 to consumable12 via tube 17. As a result of this fluid transfer, portions 18 alsofill with fluid. When a sample is to be taken, one of these portions 18is then sealed and separated from the main volume of consumable 12. Theseparated portion is then disposed within one of vials 19. Alternativelythe removable portion 18 could be disposed within one of vials 19 beforebeing sealed and removed.

Vial 110 carrying the sample is then moved to a transfer system sendermodule 111. Sender module 111 transfers vial 110 to transfer systemrouter module 112 via intermediate tube 113. Router module 112subsequently transfers vial 110 to one of a plurality of destinations114 via respective tube 115. Destinations 114 may comprise one or moreof: a lab, an automated analysis instrument, or a low temperaturestorage system. Alternatively vial 110 may be transported manually by auser.

Fluid transfer between the consumable container 12 and the bag 15 mayoccur as a result of any controllable fluid transfer method known in theart. One such method is the creation of an at least partial vacuumoutside of the consumable container 12. The flexible nature of the wallsof consumable container 12 will then cause the fluid to be drawn intoconsumable container 12. Control may be achieved by the action of apinch valve acting on tube 17, or by controlling the strength of thevacuum. Another such method is to allow the fluid to flow under theaction of gravity by putting consumable container 12 and bag 15 atdifferent heights. Once again the fluid transfer may be controlled by apinch valve acting on tube 17. Alternatively the fluid may betransferred using a non-contact pump, such as a peristaltic pump.Control of the fluid transfer is then provided by the pump itself actingon tube 17, although valves may also be used.

In the embodiment shown in FIG. 1, the fluid is purged from consumablecontainer 12 after the sample has been taken and returned tobioprocessing system 14. This is to prevent the build-up of biologicalmaterial in the consumable container 12 due to cell mortality. Thispurging of fluid from consumable container 12 may occur through any ofthe methods mentioned above. Following this it may be desirable to alsopurge tube 17 as cell mortality can lead to undesirable build-up ofbiological material in tube 17. This could be through a fluidic purge,introducing sterile fluid from an external source, or a gas purge,introducing a sterile gas from an external source. Alternatively, theperiodic aspiration and evacuation of fluid from the tube 17 ensuresthat fluid in the tube is renewed, thereby preventing the negativeeffects of cell mortality. This should be conducted at least once every4 hours. In order to achieve better washing this may be repeated morethan once in short succession, and it may also be desirable to conductthis immediately prior to sampling to ensure that the fluid in the tube17 is representative of the bulk product in bag 15.

In other embodiments of the invention, the negative effects of cellmortality are avoided by recirculating the fluid, as is shown in FIG. 2.Instead of transferring the fluid between the bag 15 and the consumablecontainer 12 via tube 17, the fluid enters the consumable container viatube 17 and returns to the bag 15 through port 26 via a different tube27. This avoids the need to purge the tube 17 and the consumablecontainer 12 and ensures that the fluid being sampled is alwaysrepresentative of the bulk product in bag 15.

Another alternative to the purging of consumable container 12 and tube17 is for the sealable, removable portions 18 to be a part of bag 15containing bulk product, the bag 15 being itself consumable. FIG. 3shows an example of such an arrangement. Here the sampling system 11 ismounted onto the bioprocessing system 14, the bioprocessing system 14applying a rocking motion to the product in bag 15. The bag 15 of FIG. 3includes a consumable container portion 12, although in some embodimentsthe entire bag 15 is consumable. One of a plurality of sealable,removable portions 18 is removed when a sample is desired to be takenand is disposed within a vial 110 ready for transport. The vial is thenmoved to transfer sender module 111 which sends the vial 110 includingsealable, removable portion 18 via tube 113. The benefit of thisarrangement is that there is no need for tubes 17 and 27, and becausethe bag 15 itself includes the consumable container portion 12 theproduct in consumable container 12 is kept moving, avoiding the negativeeffects of cell mortality.

In all embodiments of the invention the consumable container 12 willusually comprise a material suitable for biocompatibility and, as willbe seen below, in certain embodiments the consumable container 12 willcomprise a material suitable for heat sealing. Examples of possiblematerials include: ethylene-vinyl acetate (EVA), polyvinyl chloride(PVC), or polyethylene (PE). The consumable container could alsocomprise a laminate polymer construction, wherein one layer of thelaminate construction might be safe for contact with the fluid, anothermight provide a gas boundary, and one might be suitable for heatsealing. This allows for combinations of different properties to beincorporated into the material of the consumable container.

FIGS. 4a to 6d show different possible arrangements of the sealable,removable portions 18.

FIGS. 4a to 4d show an arrangement in which the removable portions 18are connected in parallel to a common transverse part 31. Thistransverse part 31 may be the consumable container 12 (or the bag 15 inembodiments where this is the consumable container) itself, with theremovable portions 18 extending outwards from the consumable container12, or the transverse part 31 may be separate from the consumablecontainer.

In FIG. 4a three of the portions 18 have been reversibly sealed, forexample by pinching, as shown by arrows 32. The arrow indicates theinflux of fluid, which then fills the open portion 33. In FIG. 4b thepreviously open portion 33 has been sealed. The sealing may occurthrough application of heat. In such embodiments, an automatic heatsealer using two heated metal plates, for example controlled by amicroprocessor, adheres opposing layers of the portions 33 together, asshown by region 34. Alternatively, a physical aseptic connector can beused to connect portions 18 to transverse part 31. In such embodiments,the connectors may be closed to seal of portions 18 which are not beingremoved, and left open to allow the portion 33 being removed to befilled with fluid. The connector would then be closed after filling.

FIG. 4c shows the portion 33 being removed. In embodiments where theportion 33 has been heat sealed this achieved by physically cuttingalong the sealed region 34, while in embodiments using a physicalconnector the portion 33 can be easily disconnected. The result ofremoving portion 33 is shown in FIG. 4d . After this step the otherportions 18 can be reopened so that the process may be repeated.

FIGS. 5a to 5d and 6a to 6d show two different arrangements of sealable,removable portions 18 connected in series, FIGS. 5a to 5d showing thearrangement when portions 18 are sealed using heat and then separatedfrom the consumable container 18, whilst FIGS. 6a to 6d show thearrangement when portions 18 are connected to the consumable container18 using physical aseptic connectors.

The first step of taking a sample when the portions 18 are sealed usingheat is shown in FIG. 5a . A region 41 of consumable container 12 isfilled with fluid, as shown by the arrow in the figure. Region 41 couldextend from the consumable container 12, or it could be the consumablecontainer 12 itself.

FIG. 5b shows the step of sealing off a sampling portion 42 from theregion 41. The sampling portion shown is illustrative, and need not bean end of the region 41. It could instead be, for example, a corner ofthe region 41. As shown in FIG. 5c the sampling portion 42 is thenseparated from the region 41, for example by cutting.

After the sampling portion 42 has been separated from the region 41, theregion 41 is purged, as shown by the arrow in FIG. 5d . The process maythen be repeated.

The first step of taking a sample when the portions 18 are connectedusing physical connectors is shown in FIG. 6a . A region 51 ofconsumable container 12 is filled with fluid, as shown by the arrow inthe figure. Region 51 could be the consumable container 12 itself, buttypically takes the form of a string of sampling portions linkedtogether by physical connectors connected to the consumable container 12at one end.

In FIG. 6b a sampling portion 52 is sealed off from region 51 by closinga physical connector, and the sampling portion 52 is then separated fromregion 51 in FIG. 6c . Finally, in FIG. 6d the region 51 is purged inorder that the process might be repeated, as shown by the arrow in FIG.6 d.

As mentioned earlier the samples taken from the consumable container 12are disposed within vials, and an example of this is shown in FIGS. 7ato 7d . In FIG. 7a the sampling portion 61 is disposed in the vial 62before the sample is taken. The sampling portion 61 is disposed in thevial 62 through a region 63 of the lid 64 of the vial, leaving a region65 of the consumable container outside of the vial. The sampling portionis then aspirated as shown by the arrow in FIG. 7 a.

In the step shown in FIG. 7b heat is applied to the region 63. Thisseals the sampling portion 61 off from the region 65 of the consumablecontainer, and also acts to integrate the sampling portion 61 with thevial 62 via lid 64. The composite 66 of the vial and the samplingportion is then separated from the region 65 in the step shown in FIG. 7c.

Removing the lid 64 from a composite vial 66 will serve to allow accessto the sample, and this is illustrated in FIG. 7d . The region 63 issealed to the portion 61 when heat is applied. Therefore, when the lid64 is removed from the composite vial 66 the seal is broken, allowingaccess to the sample.

An alternative means of disposing the samples in vials is shown in FIGS.8a-8e . The sampling vial 70 shown in FIG. 8a comprises an extended part71 of the consumable container, a vial body 72, and a lid 73. Theextended part 71 is attached to the lid 73, and the sampling vial 70 istherefore supplied attached to the consumable container. FIG. 8b showsthe sampling vial 70 after it has been aspirated with a sample.

In the step shown in FIG. 8c heat has been applied to region 74 of theextend part 71, thereby sealing off the sampling vial from the bulkproduct in the consumable container. In FIG. 8d the sampling vial 70 hasbeen separated from the consumable container, which is typicallyachieved by cutting. The sampling vial 70 may now be transported, andthe sample accessed by removing the lid 73 from the vial body 72, asshown in FIG. 8 e.

FIG. 9 shows separable portions 94 as part of a bioprocessing system.The system includes a bulk fluid container 91, which may be abioprocessing bag such as a GE Wave bag. A tube 92 circulates fluidreceived from the bulk fluid container 91 by means of a peristaltic pump93. The separable portions 94 then collect the fluid from the tube 92.The separable portions 94 comprise an analytics region to enableautomated analysis in situ by the analytics module 95.

FIG. 10 shows an embodiment of a separable portion 100 connected to amain loop 101. The main loop receives and circulates fluid from a bulkfluid container, and this fluid is then collected by one or moreseparable portions 100. A sample loop 102 is connected to the main loop101 via an inlet valve 102 a and an outlet valve 102 b. Disposed on themain loop 101 between the valves 102 a and 102 b is a valve 101 a.Adjacent to the input end of the sample loop is a thermal weld 103 aseparating the sample loop from drive fluid 103.

An analytics region is separated from the sample loop by a thermal weld104 a disposed adjacent to the output end of the sample loop. Theanalytics region comprises a labelling region 104 b, a detection region104 c, and a waste region 104 d. The labelling may be done by dyes,antibodies, or PCR prep, and these reagents may be included on the chip,or the reagents could be provided by a separate instrument.

The valves 101 a, 102 a and 102 b and the drive fluid 103 are typicallycoupled to actuators in a separate analytics module. These actuators maybe pneumatic or electromechanical. The analytics module also includes adetection system coupled to the detection region 104 c, for example anoptical detector and emitter.

FIG. 11 shows the separable portion 100 in operation. In the first step,bioprocess fluid fills the main loop 101, but cannot enter the separableportion because the valves 102 a and 102 b are closed. In step 2, themain loop valve 101 a is closed and the valves 102 a and 102 b areopened, allowing fluid to enter the sample region 102. The valves 102 aand 102 b or other actuators in a similar location then heat seal andcut the separable portion 100 in step 3, disconnecting it from the mainloop. In step 4, the main loop 101 can then be purged, for example bypumping through gas from the headspace. However, step 4 may, in someembodiments, be skipped. In step 5, the drive fluid 103 is compressedwith an actuator, breaking the heat seal 103 a and causing the fluid inthe sample region to break heat seal 104 a and flow into the analyticsregion 104. The fluid flows via labelling region 104 b, where itcollects reagents such as dyes, into detection region 104 c. In step 6,the fluid in the detection region is analysed.

FIG. 12 shows an alternative embodiment of a separable portion 120 wherethe sample fluid fills a flexible dead end sample region 122. This isachieved by closing a valve 121 a, provided on the main loop 121downstream of the input end of the sample region 122, and opening avalve 122 a in the separable portion to allow the sample region 122 toinflate. The valve 122 a in the separable portion can then be closed,heat sealed, and cut. The sample can then be compressed with an actuatorbreaking a heat seal 124 a and causing the fluid to flow into thelabelling region 124 b as before.

1. (canceled)
 2. The consumable container of claim 17, wherein the oneor more sealable portions are sealed by application of heat to an areabetween a removable portion of the one or more sealable portion and aremainder of the consumable container.
 3. (canceled)
 4. The consumablecontainer of claim 17, wherein the consumable container comprises a heatsealable material.
 5. (canceled)
 6. (canceled)
 7. The consumablecontainer of claim 17, wherein the consumable container comprises abiocompatible material.
 8. The consumable container of claim 17, whereinthe consumable container comprises at least one of: ethylene-vinylacetate (EVA), polyvinyl chloride (PVC), or polyethylene (PE).
 9. Theconsumable container of claim 17, wherein the consumable containercomprises a laminated polymer construction.
 10. (canceled) 11.(canceled)
 12. (canceled)
 13. (canceled)
 14. (canceled)
 15. (canceled)16. (canceled)
 17. A consumable container for filling with a fluid in abioprocessing process is provided, the consumable container comprising:one or more sealable portions, such that one or more samples of thefluid may be taken by sealing one or more of said one or more sealableportions; wherein at least one of the one or more sealable portionscomprises an analytics region.
 18. The consumable container of claim 17,wherein the one or more sealable portions are removable.
 19. Theconsumable container of claim 17, wherein the analytics region containsreagents.
 20. The consumable container of claim 17, wherein the one ormore sealable portions each comprise a sample region having an input endfor receiving fluid and an output end, the sample region being connectedto the analytics region.
 21. The consumable container of claim 20,wherein the input end of the sample region is configured to receivefluid from a main portion of the consumable container and the output endis configured to return fluid to said main portion.
 22. The consumablecontainer of claim 21, wherein a valve is disposed on the main portionbetween the input end of the sample region and the output end of thesample region, such that fluid is directed into the sample region whenthe valve is closed.
 23. The consumable container of claim 22, whereinthe analytics region is connected to the sample region via an inletdisposed between the input end of the sample region and the output endof the sample region.
 24. The consumable container of claim 20, whereinthe input end of the sample region is configured to receive fluid from amain portion of the consumable container and the analytics region isconnected to the sample region at the output end of the sample region.25. A system comprising: a reusable part; a bulk fluid container; and aconsumable container for filling with a fluid in a bioprocessingprocess, the consumable container comprising: one or more sealableportions, such that one or more samples of the fluid may be taken bysealing one or more of said one or more sealable portions; wherein atleast one of the one or more sealable portions comprises an analyticsregion, wherein the consumable container is arranged to be fluidlyconnected in use to the bulk fluid container such that the consumablecontainer may be filled with a sample of the fluid from the bulk fluidcontainer.
 26. The system of claim 25, wherein the one or more sealableportions are removable, further comprising means for purging theconsumable container and returning the fluid to the bulk fluid containerafter the one or more sealable portions have been removed.
 27. Thesystem of claim 25, wherein fluid can be transferred between the bulkfluid container and the consumable container at least partially throughthe creation of a vacuum.
 28. The system of claim 25, wherein fluid canbe transferred between the bulk fluid container and the consumablecontainer at least partially through the action of gravity bypositioning the consumable container below the level of the fluid in thebulk container.
 29. The system of claim 25, wherein fluid can betransferred between the bulk fluid container and the consumablecontainer at least partially through the use of a pump.
 30. The systemof claim 29, wherein the pump is a peristaltic pump.
 31. A system forprocessing biological samples, comprising: a first processing stationhaving an outlet; a second processing station having an inlet; and apumped fluidic channel connecting said outlet to said inlet, wherein thesecond processing station comprises a consumable container, wherein theconsumable container for filling with a fluid comprises: one or moresealable, removable portions, such that one or more samples of the fluidmay be taken by sealing and removing one or more of said one or moresealable, removable portions, wherein at least one of the one or moresealable, removable portions comprises an analytics region.